The present invention relates to the study of pathological changes in the gastrointestinal system, and more particularly to an apparatus for taking intestinal samples as well as to the use thereof.
Among the various techniques that are used today to study pathological changes in the gastro-intestinal system are X-ray contrast examination, computerized tomography and magnetic resonance tomography. Endoscopy, i.e. insertion into the gastrointestinal tract of a stomach or intestinal viewer (gastroscopy, colonoscopy, rectoscopy) makes it possible to inspect the intestinal wall and to take samples from the intestinal mucous membrane (biopsy) which then may be examined by e.g. microscopy. Recently, also intestinal perfusion systems have been used. All these techniques are expensive, time-consuming and more or less trying to the patient. There is therefore a need for a simple methodology that makes it possible to study pathological processes in the intestinal mucous membrane without using biopsy or perfusion.
WO 95/32668 discloses a rectal instrument to be used in allergy diagnosis and designed for insertion into the colonic tract to take samples from the lumen of the large intestine after provocation of the mucous membrane with an allergen. The instrument comprises a tube-like element having a terminal part that is expandable, specifically an inflatable balloon. Subareas on the balloon have a diffusable allergen absorbed or adsorbed thereto, and on the same or separate subareas, a receptor(s) for one or more inflammation markers, usually antibodies specific to the relevant marker(s), are bound to the balloon. The instrument is inserted into the rectum, whereupon the balloon is inflated such that the outer surface of the balloon contacts the mucous membrane. The allergen diffuses to the rectal mucous membrane and, if the individual concerned is allergic to the allergen in question, will cause the release of inflammation markers which in turn diffuse to the lumen where they eventually are captured by the receptor(s) on the balloon surface. After the marker or markers have been released and bound to the balloon, the balloon is deflated and the device is removed and analyzed with respect to the bound marker(s).
The above instrument has, however, the drawback that the areas with diffusible allergen and the areas with immobilized receptor on the balloon surface may be damaged by contact with the internal sphincter when inserted and retracted through the patient""s anus. It may also be mentioned, that, generally, immobilizing receptors on the balloon surface could cause problems in that hazardous residues from the coupling of the receptor(s) may remain on the surface.
The present invention aims at overcoming the disadvantages of the prior art devices or instruments and provide an apparatus for rectal insertion for studying pathological processes in the intestinal mucous membrane without the use of biopsy or perfusion. Like the instrument described in WO 95/32668 above, the apparatus of the present invention is based on contacting an expandable part thereof with the intestinal wall for sampling, and optionally also for provocation of the intestine with allergen.
According to a basic concept of the invention, however, the sampling area(s) and provocation area(s), when present, of the expandable part essentially are protected from contact with the intestinal wall when the expandable part is inserted and retracted from the colon through the patient""s anus.
The present invention therefore provides an apparatus for taking an intestinal sample in a human or animal patient, comprising a holder part and an expandable part supported by the holder part and having at least one sampling area. In a non-expanded state of the expandable part, the expandable part is rectally insertable, and in an expanded state, the sampling area or areas of the expandable part are capable of contacting the intestinal wall. The apparatus is characterized in that it comprises means for protecting the sampling area or areas from contact with the intestinal wall and intestinal fluid when the expandable part in its non-expanded state is rectally inserted into the intestinal tract.
Preferably, the apparatus comprises means for protecting the sampling area or areas also when removing the expandable part from the intestine.
While essentially the whole area of the expandable part could be a sampling area, it is preferred that one or preferably, more subareas thereof are used as sampling areas and provocation areas.
The sampling area or areas on the expandable part may have one or more receptors for, for example, an inflammation or cancer marker or the like bound to the. surface thereof (similarly as in the device described in WO 95/32668 above). Such inflammation markers may, for example, be derived from neutrophilic granulocytes, eosinophilic granulocytes, mast cells/basophilic granulocytes, or may be a cytokine, a prostaglandin or a plasma protein, such as albumin.
While the sampling area or areas in this case may have the receptor(s) immobilized directly to the surface of the expandable part, it is preferred that the sampling area or areas comprise a surface element of suitable material attached to the expandable part surface. Such a material may exhibit a two-dimensional surface to which the receptor or receptors are immobilized, or constitute a three-dimensional matrix structure in which the receptor or receptors are immobilized in depth.
Alternatively, and at least in some aspects also preferably, the sampling area or areas comprise absorbing material (without any immobilized receptor) capable of effectively sucking up water and substances dissolved therein (such as proteins, enzymes, hormones etc) when contacted with the intestinal mucosa, such that the content of such substances in the absorbed material may be analyzed. After sampling, a reactant or reactants may be added directly to the absorbing material to detect the presence of a certain substance or substances through a colour reaction or similar.
Usually, however, the absorbing material is removed from the expandable part after sampling and the absorbed substances extracted and analyzed separately by various analytical methods, such as electrophoresis, radioimmunological techniques, enzyme immunosorbent assay (ELISA) or nephelometry, just to mention a few.
While it is within the scope of the present invention that the apparatus may be designed for sampling at arbitrary sites along the intestinal tract, it is presently preferred to take samples in the lumen of the large intestine. Such sampling may, for example, advantageously be used for testing for markers for allergy, especially food allergy including e.g. celiac disease, after provoking the colonic mucosa with a desired allergen(s), e.g. gluten (as described in the above-mentioned WO 95/32668).
The expandable part is advantageously an inflatable member of a flexible or elastic material, for example a balloon or an elastic tubular member.
In one embodiment of apparatus according to the present invention, the sampling area or areas on the expandable part are protected by a protective cover until the expandable part has reached the desired section of the intestine to be studied. Prior to or after expanding the expandable part, the cover is removed, e.g. mechanically by pulling means provided on or associated with the apparatus part outside the body, to permit sampling by contacting the sampling area or areas with the intestinal wall.
In another embodiment, the sampling area or areas on the expandable part are protected by a cover which may be opened in connection with the sampling and then be re-closed over the sampling area(s) after the sampling is completed. Such a cover may, for example, be of capsule or shell type, for instance a two-part shell or capsule wherein the two parts together, preferably with some overlap, cover the sampling area(s) in the non-expanded state of the expandable part, but which are removed from and expose the sampling area(s) in the expanded state.
In still another embodiment, the expandable part is displaceably mounted (e.g. telescopically) within the holder part of the apparatus so that the expandable part is kept within the holder part during the rectal insertion and retraction of the apparatus, and brought out of the holder part at the test site to be expanded. In yet another embodiment, the sampling area or areas on the expandable part are depressed in relation to the remaining surface of the expandable part when the latter is in its non-expanded state to thereby prevent contact with the intestinal wall. If, for example, the expandable part is a balloon or elastic tube or cylinder with sampling elements on the surface, the holder part supporting the balloon or elastic tube may have a recess or recesses for receiving each sampling element when the balloon is deflated.
Like the apparatus described in WO 95/32668, the expandable part may also comprise means for allergen presentation to provoke the intestine before the sampling.
Such means may be the surface itself of the expandable part or a special element(s) having the allergen(s) diffusively bound or adsorbed thereto. The allergen-presenting area(s) will, of course, also be protected by the protective means at the same time as the sampling area(s). Optionally, the allergen-presenting area or areas may be the same as the sampling areas.